Identification of trichostatin A as a novel transcriptional up-regulator of scavenger receptor BI both in HepG2 and RAW 264.7 cells.
Scavenger receptor class B type I (SR-BI) and its human homologue CLA-1 plays an important role in reverse cholesterol transport (RCT). Using a previously established cell-based CLA-1 up-regulator screening assay, one of the positive strains, 04-9179, presented potent activity in elevating CLA-1 transcriptional level. We report here the identification of an active compound 9179A as a known compound trichostatin A (TSA), and its effects on CLA-1/SR-BI expression both in HepG2 human hepatoma cells and RAW 264.7 murine macrophage cells in vitro. The results showed that the mRNA and protein level of CLA-1/SR-BI were significantly up-regulated by 9179A both in HepG2 and RAW 264.7 cells. Corresponding to this, the uptake of DiI-HDL by both cells and the efflux of [(3)H]cholesterol by RAW 264.7 cells were increased by 9179A in dose-dependent manner. ABCA1 was also increased but SR-A decreased by 9179A in RAW 264.7 cells. Using a combination of reporter assays with various deletion in CLA-1 promoter and electrophoretic mobility shift assay, we demonstrated that -419/-232 bp fragment of the CLA-1 promoter mediated the effects of 9179A (i.e., TSA). Together, these studies identified TSA as a novel up-regulator of CLA-1/SR-BI both in HepG2 and RAW 264.7 cells.
Bao
Yi
Y
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
Yang
Yuan
Y
Wang
Li
L
Gao
Lei
L
Jiang
Wei
W
Wang
Lifei
L
Si
Shuyi
S
Hong
Bin
B
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D017930:Genes, Reporter; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection; D015854:Up-Regulation
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012333:RNA, Messenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; C012589:trichostatin A; D006655:Histone Deacetylases